Four new regions on the human genome that have been identified are associated with Behçet''s disease, which causes inflammation of blood vessels in various parts of the body.
Behçet''s disease is triggered by complex genetic and environmental factors and common symptoms include painful mouth and genital sores, and eye inflammation that can lead to blindness.
Scientists at the National Human Genome Research Institute (Bethesda, MD, USA) conducted a genome-wide association study (GWAS) that enrolled 1,209 Turkish people affected by Behçet''s disease and 1,278 unaffected Turkish people, all of whom were indigenous residents of the country. The team looked at single-nucleotide polymorphisms (SNPs) on the human genome, with each SNP representing a difference in a single DNA building block and compared SNP differences between people with and without disease.
From nearly 800,000 SNPs, the investigators detected and mapped a small number that are found in those who have Behçet''s disease at a significantly higher rate than in those without the disease, suggesting that the variant or another one nearby contributes to the disease. As not all the SNPs were genotyped, the team used the strategy of imputing, or surmising, that there were genotypes worth investigating near known variants.
An important association was found between Behçet''s disease and a gene called endoplasmic reticulum aminopeptidase 1 (ERAP1) which codes for a molecule that processes microbial proteins in white blood cells. A significant association of Behçet''s disease with variants near the chemokine (C-C motif) receptor 1 (CCR1) gene was also noted. Proteins coded by this gene help infection-fighting blood cells migrate to sites of invading microorganisms. An association of the disease was found with variants in the killer cell lectin-like receptor subfamily C, member 4 (KLRC4) gene and the signal transducer and activator of transcription 4 (STAT4) gene, in which different variants in the same vicinity of the genome increase risk for autoimmune diseases, including rheumatoid arthritis and lupus.
The four newly identified gene regions were already known to play a role in immune regulation. The genetic associations have helped classify Behçet''s disease with more common inflammatory conditions such as psoriasis, inflammatory bowel disease, and a form of spinal arthritis called ankylosing spondylitis. Elaine F. Remmers, PhD, a coauthor of the study said, "Each of the genetic factors may contribute a little to the overall risk of disease. We are also identifying them in pathways that are important in inflammatory disease development." The study was published on January 6, 2013, in the journal Nature Genetics.